Biomedical subjects

Kuo-Wei Chang

Publications and source records attributed to Kuo-Wei Chang.

32 records · Page 2Linked to original sources

PubMed2004

Association of CTLA-4 gene polymorphism with oral submucous fibrosis in Taiwan.

BACKGROUND: Oral submucous fibrosis (OSF) is an insidious, pre-cancerous, chronic disease that may affect the entire oral cavity and sometimes extend to the pharynx. It has been reported to be associated with immune function. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4; CD (cluster of differentiation) 152) is a negative regulator of T-lymphocyte activation. Particular genotypes of the locus encoding the CTLA-4 glycoprotein have been associated with susceptibility to various autoimmune diseases. This study was designed to investigate the role of CTLA-4 polymorphism in susceptibility to OSF. METHODS: We genotyped 62 patients with OSF and 147 healthy controls for allelic determinants at the exon 1 +49 polymorphism site by restriction fragment length polymorphism. Genotype and phenotype frequencies were evaluated with Chi-squared test. RESULTS: The G allele at position +49 of exon 1 was significantly associated with OSF. The frequency of A/A homozygotes was higher in controls than in patients (17.0% vs. 3.2%; chi(2) = 7.65, P = 0.02); the G phenotype was more frequent in patients than in controls (96.8% vs. 83.0%; chi(2) = 9.31, P = 0.002). Compared with controls, the G allele genotype and phenotype frequencies were increased in patients with OSF. CONCLUSION: This is the first report that the CTLA-4 +49 G allele confers an increased risk of OSF in Taiwan.

Adenine↗

PubMed2004

Polymorphism of the MICA gene and risk for oral submucous fibrosis.

BACKGROUND: Oral submucous fibrosis (OSF), an insidious, pre-cancerous, chronic disease that may affect the entire oral cavity and sometimes extend to the pharynx has been reported to be associated with immune function. The major histocompatibility complex (MHC) class I chain-related gene A (MICA) is expressed by keratinocytes and other epithelial cells, and its encoded protein interacts with gamma/delta T-cells localized in the submucosa. The MICA gene has a triplet repeat (GCT) polymorphism in the transmembrane domain resulting in five distinct allelic patterns. METHODS: We analyzed MICA polymorphism in 80 OSF patients and 351 randomly selected unrelated controls by using the ABI Prism 377-18 DNA sequencer (Applied Biosystems) to analyze the sample DNA PCR products. The number of microsatellite repeats was estimated with Genescan 672 software (Applied Biosystems) with a standard size marker of GS-350 TAMRA. RESULTS: The phenotype frequency of allele A6 of MICA in subjects with OSF was significantly higher than that in controls (OR = 3.48; 95% CI = 1.8-6.71; P = 0.0002), as was the frequency of the allele (OR = 2.65; 95% CI = 1.44-4.86; P = 0.001). CONCLUSION: The results suggest that allele A6 in MICA might confer a risk for OSF.

Adult↗

PubMed2004

The molecular markers for prognostic evaluation of areca-associated buccal squamous cell carcinoma.

BACKGROUND: Buccal squamous cell carcinoma (BSCC) is the most frequently occurring oral cancer in Asians due to the popularity of areca use in this area. The aim of the present study was to evaluate the survival of areca-associated BSCC associated with multiple molecular markers. METHODS: Using immunohistochemistry, we evaluated the survival of a cohort of 55 patients with BSCC being followed long term, as correlated to the expression of variable markers. RESULTS: We found that p53, p21, Rb, cyclin D1 (CCD1), MDM2, and gamma-catenin were positive in 81, 60, 70, 31, 88, and 44% of patients, respectively. Subjects with -ve immunoreactivity for CCD1, and +ve immunoreactivity for MDM2 and gamma-catenin had significantly better survival than subjects with the opposite immunoreactive pattern. KAPLAN-meier survival curves confirmed this association. CONCLUSION: The data indicate that expression of CCD1, MDM2, and gamma-catenin might serve as potential prognostic markers for BSCC in areca-using patients.

Adult↗

PubMed2004

Correlation between functional genotypes in the matrix metalloproteinases-1 promoter and risk of oral squamous cell carcinomas.

BACKGROUND: Oral squamous cell carcinoma (OSCC) and oral submucous fibrosis (OSF), which are highly associated with areca use, are prevalent in most Asian countries. Matrix metalloproteinases (MMPs) are superfamily of metal-dependent proteolytic enzymes, mediating the degradation of extracellular matrix. Insertion/deletion (-1607 2G-->1G) polymorphism has been described in the promoter region of the human matrix metalloproteinases-1 (MMP-1) genes, which cause an alteration in the transcriptional activity. This genotype is associated with risks of cancer genesis and metastasis. In this paper, we studied the relationship between such genotype and areca-associated oral diseases. METHODS: Genomic DNA from the blood of OSCC (n = 121), OSF (n = 58) cases and controls (n = 147) were amplified by polymerase chain reaction (PCR)-based genotyping. The OSCC were further grouped into buccal squamous cell carcinoma (BSCC) and non-buccal suqmaous cell carcinoma (NBSCC), in accord with the site of involvement. The significance of the differences was assessed by Fisher's exact test. RESULTS: The 2G genotype in MMP-1 promoter was observed with a higher frequency in both OSCC (0.69, P = 0.06) and NBSCC (0.76, P = 0.03) cases compared with controls (0.63), with an odds ratio of 2.17 and 4.58, respectively. This genotype was not related to the risk of OSF. No other clinicopathologic parameter was associated with the genotypes in OSCC cases. CONCLUSION: The results showed that 2G genotype in MMP-1 promoter was associated with the risk of OSCC.

Adult↗

PubMed2004

Functional genotype in matrix metalloproteinases-2 promoter is a risk factor for oral carcinogenesis.

BACKGROUND: Matrix metalloproteinase-2 (MMP-2) can degrade extracellular matrix and basement membrane, and play an important role in the development and progression of multiple carcinomas, including oral squamous cell carcinoma (OSCC). A -1306C-->T polymorphism in the MMP-2 promoter disrupts Sp1-binding site, and results in reduction of transcriptional activity. This study aimed to assess the association of such genotype with the risk of OSCC and oral submucous fibrosis (OSF), which is a precancerous condition that exhibits excessive collagen production and etiologically links to areca use. METHODS: Genomic DNA from the blood samples of 121 OSCC cases, 58 OSF cases and 147 controls were amplified by polymerase chain reaction (PCR) and subjected to denaturing high-performance liquid chromatography (dHPLC) analysis for genotyping. The OSCC were further classified into buccal squamous cell carcinoma (BSCC) and non-buccal squamous cell carcinoma (NBSCC), according to the site of involvement. Fisher's exact test and unconditional logistic regression models were used for statistical analysis. RESULTS: Subjects carrying CC genotype had nearly twofold increased risk for developing OSCC when comparing with CT or TT genotype. Subjects carrying CC genotype had more apparent risk (greater than fourfold) for developing NBSCC. However, no increase in risk for lymph node metastasis or advanced stage was identified in OSCC cases carrying such genotype. Preliminarily data suggest no significant association between subjects carrying CC genotype and the development of BSCC or OSF. CONCLUSION: This is the first paper demonstrating that functional genotype of MMP-2 promoter is a risk factor for oral carcinogenesis, particularly for the subsets occurring on non-buccal site.

Adult↗

PubMed2003

Cyclin D1 genotype in areca-associated oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common malignancy in areca-chewing regions, accounting for up to 50% of malignant tumors in some South Asian countries. Amplification and/or over-expression of cyclin D1 (CCND1) is a frequent event in human malignancies, including OSCC. CCND1 G870A polymorphism (codon 242) gives rise to two isoforms of the protein. The objective of the present study was to evaluate if the risk, onset, and prognosis of areca-associated OSCC is related to CCND1 genotypes. METHODS: We analyzed the CCND1 genotype in 70 OSCC cases and 93 control Taiwanese using single-strand conformation polymorphism techniques. RESULTS: Statistical analysis showed that CCND1 genotype had no impact on the risk, onset, or survival of areca-associated OSCC. However, buccal squamous cell carcinoma (BSCC) appeared to be less frequently associated with AA genotype than non-BSCC (P = 0.02). In addition, amplification of CCND1 was significantly more prevalent in OSCC cases (22%) than in control subjects (2%, P < 0.01). CONCLUSION: This study demonstrates that the CCND1 genotype may confer different risks for BSCC and non-BSCC.

Adult↗

PubMed2003

Modulation of KGF-1 gene expression in oral fibroblasts by ripe areca nut extract.

BACKGROUND: Areca chewing is a common habit of Asians, leading to a high propensity for a variety of oral diseases in this population. This research aimed to study the expression level of genes in oral fibroblast cell lines in response to exposure to ripe areca nut extract (rANE). METHODS: Fifteen oral fibroblast cell lines obtained from individuals aged 20-77 years were established. Treatment of a cell line with 40 micro g/ml rANE for 24 h was performed to achieve RNA for cDNA microarray analysis. RESULTS: Among some 320 genes exhibiting detectable expression levels, 14 were up-regulated and 26 were down-regulated more than 2.5-fold. Semi-quantitative RT-PCR analysis suggested that up-regulation of IL-6 expression and down-regulation of PDGFR, APP-1 and KGF-1 expressions in multiple cell lines assayed, were compatible with the results of the microarray analysis. Using quantitative real-time RT-PCR analysis, a remarkable down-regulation of KGF-1 expression in response to 40 microg/ml rANE, ranging 1.5-ninefold as compared to controls, was found in 60% (9/15) of the cell lines. CONCLUSION: This study established a novel toxicogenomic database for rANE. The down-regulation of KGF-1 expression in oral fibroblast cell lines potentially impairs the proliferation of overlying keratinocytes, which could partially explain the frequent epithelial atrophy observed in chronic areca chewers in vivo.

Adult↗

PubMed2003

Elevated expression of cyclooxygenase (COX)-2 in oral squamous cell carcinoma--evidence for COX-2 induction by areca quid ingredients in oral keratinocytes.

BACKGROUND: Elevated expression of cyclooxygenase (COX)-2 has been demonstrated in several human cancers. Whether COX-2 is up-regulated in areca quid (AQ) related oral squamous cell carcinoma (OSCC) is unknown and the potential of AQ ingredients to induce COX-2 expression has not been studied. METHODS: COX-2 expression was analyzed by immunohistochemistry and RT-PCR in oral tissues. The COX-2 mRNA and protein induction potential of AQ ingredients were analyzed by real-time RT-PCR and Western blotting in normal human oral keratinocyte (NHOK). RESULTS: COX-2 protein expression was significantly higher (P < 0.01) in OSCC (n = 27) as compared to their adjacent non-cancerous matched tissue (NCMT). COX-2 protein was nearly undetectable in control normal oral mucosa. The level of COX-2 mRNA was markedly elevated in 63% (12/19) of OSCC compared to NCMT. Hydroxychavicol induced COX-2 mRNA and protein expression in NHOK. CONCLUSIONS: COX-2 protein as well as mRNA expression were significantly enhanced in OSCC as compared to NCMT. Hydroxychavicol, a unique ingredient in AQ, induced COX-2 expression in NHOK, which highlighted early involvement of COX-2 in AQ-associated oral oncogenesis.

Areca↗

PubMed2003

The biphasic differential expression of the cellular membrane protein, caveolin-1, in oral carcinogenesis.

BACKGROUND: The increased expression of Cav-1 is seen in various cancers from prostate, esophagus, colon, breast and pancreas yet the information regarding the correlation between the expression of Cav-1 and oral cancer is blind. Thus, the expression profile of caveolin-1 (Cav-1) in oral carcinogenesis and the correlation to the clinicopathologic covariates are examined in this study. METHODS: Immunohistochemistry was used to detect Cav-1 expression in non-cancerous matched tissues (NCMT; n=12), and tissue from normal oral mucosa (NOM; n=12), oral pre-cancer lesions (OPL; n=17), primary oral squamous cell carcinoma (POSCC; n=47) and metastatic OSCC (MOSCC; n=8). The Cav-1 expression was correlated to the age, site, areca use, stage, size, nodal involvement, and differentiation stage. Western blot was used to confirm the specificity of antibody and to follow changes in Cav-1 expression. RESULTS: The Cav-1 immunoreactivity increased significantly from 8% in NOM and 17% in NCMT to 53% in OPL and 79% in POSCC. In addition, lymph node metastasis (LNM) was present in 62% of Cav-1(+) POSCCs, but only in 10% of Cav-1(-) POSCCs. Remarkably, only 38% of MOSCCs had Cav-1 immunoreactivity. CONCLUSION: An increased Cav-1 expression is seen in the stepwise carcinogenesis from NOM, NCMT, OPL to POSCC. The decrease in expression from the POSCC to MOSCC indicates the value to explore its biphasic functions in oral carcinogenesis. Whether Cav-1 is an important predictor or prognosis for survival still awaits the extension of clinical follow-up.

Adult↗

PubMed2003

The increase of voltage-gated potassium channel Kv3.4 mRNA expression in oral squamous cell carcinoma.

BACKGROUND: Potassium channels have been reported to be involved in the proliferation of many types of cells, including tumor cells. The overexpression of the K+ channel and related channel activity are involved in the neoplastic process. METHODS: We examined the expression of an A-type voltage-gated K+ channel, Kv3.4, in oral squamous cell carcinoma (OSCC) and esophageal squamous cell carcinoma (ESCC) compared with non-cancerous matched tissue (NCMT) using RT-PCR analysis. In addition, administration of an A-type K+ channel blocker, 4-aminopyridine (4-AP), and an antisense oligodeoxynucleotide (ODN) directed specifically against Kv3.4 were performed to identify the involvement of Kv3.4 in the growth of OSCC cells. RESULTS: A significantly increase in the frequency of Kv3.4 mRNA expression was identified in OSCC (64%) compared to corresponding NCMT (29%) (P = 0.05). The increase of Kv3.4 mRNA expression was also eminent in ESCC. Growth of OSCC cells was significantly inhibited by 4-AP in a dose-dependent manner at different time point of treatment. In OECM-1 OSCC cells, a significant growth inhibition was noted in antisense ODN-treated cells compared to control cells. CONCLUSION: We provide novel evidences of the increase of Kv3.4 mRNA expression in OSCC. The abrogation of Kv3.4 inhibits the growth of OSCC cells.

4-Aminopyridine↗

PubMed2002

Multiple molecular alterations of FHIT in betel-associated oral carcinoma.

To determine the alterations of the FHIT (fragile histidine triad) gene in oral squamous cell carcinoma (OSCC), this study examined mutation, promoter methylation, mRNA transcription, and protein expression of FHIT in OSCC associated mostly with the use of betel and/or tobacco. Analyses of the coding exons (exons 5-9) identified a deletion of one base in intron 4 in one tumour and a deletion of exon 7 in two tumours. Using bisulphite genomic sequencing, 28% of the informative subjects exhibited promoter methylation. An aberrant FHIT transcript spanning from exon 3 to exon 10, which was verified by RT-PCR analysis, was identified in 36% of the OSCC subjects, 50% of the oral pre-invasive lesions, and 5% of the non-cancerous match tissue. An abnormal immunohistochemical level of Fhit was detected in 41% of OSCC subjects. A statistically significant association was found between aberrant transcription of the FHIT gene and an abnormal level of Fhit immunoreactivity. The results indicated that alteration of FHIT is a frequent occurrence in OSCC and thus suggests that the aberrance in FHIT transcription could be an early event of oral carcinogenesis.

Acid Anhydride Hydrolases↗

PubMed2002

Regulation of IGFBP-5 expression during tumourigenesis and differentiation of oral keratinocytes.

To identify molecular events involved in the pathogenesis of oral squamous cell carcinoma (OSCC), genes differentially expressed in OSCC and non-cancerous matched tissue (NCMT) samples were analysed using a subtractive hybridization strategy. NCMT-enriching clones that have been linked to suppressor pathway in previous studies were subjected to advanced analyses. Complete absence of insulin-like growth factor binding protein-5 (IGFBP-5) expression at both the mRNA and the protein level was identified in nearly all (5/6) OSCC cell lines with the exception of the SCC25 cell line, which exhibited high IGFBP-5 expression. However, this protein is consistently present in cultured normal human oral keratinocytes (NHOKs). Immunohistochemistry revealed moderate to strong cytoplasmic immunoreactivity of IGFBP-5 in the stratum spinosum and stratum granulosum in the vast majority of NCMT samples. A remarkable reduction in IGFBP-5 immunoreactivity was detected in 56% (26/46) of OSCC samples, compared with the corresponding NCMT (p < 0.0001). Induction of differentiation in both NHOKs and SCC25 up-regulated IGFBP-5 expression. Administration of a green tea compound with anti-cancer properties, (-)-epigallocatechin 3-gallate, at a concentration of 5-20 micro g/ml also up-regulated IGFBP-5 expression in NHOKs in a dose-dependent manner. The findings suggest that IGFBP-5 may be an important factor in the differentiation of oral keratinocytes and that down-regulation of IGFBP-5 may be involved in the neoplastic transformation of oral keratinocytes.

Antineoplastic Agents↗

PubMed2002

The retinoic acid receptor-beta (RAR-beta) mRNA expression in the oral squamous cell carcinoma associated with betel quid use.

BACKGROUND: Within the abundant retinoids nuclear receptors, abnormally low expression of the RAR-beta has been shown to contribute to neoplastic progression in oral epithelium in western countries. Distinctly different risk factors contributing to oral squamous cell carcinoma (OSCC) in epidemiologically different societies denote the value of exploring the role of RAR-beta expression in OSCC associated with betel quid (BQ) use in our society. METHODS: We examined the cellular expression of RAR-beta using in situ hybridization (ISH) analysis on 38 pairs of surgical specimens of primary OSCC and non-cancerous matched tissues (NCMT) to correlate with their clinico-pathological features including age, sites of tumor, habit of BQ use, stage, size of primary tumor, lymph node metastasis, differentiation. RESULTS: Of all cases analyzed, BQ users were significantly younger than non-BQ users (51.2 +/- 2.1 vs. 60.2 +/- 2.6, P = 0.01). 52% OSCC of BQ users (13/25) and 23% OSCC of non-BQ users (3/13) exhibited the absence of RAR-beta expression. In 17 paired-samples from buccal mucosa (BM), most NCMT and less than half of OSCC exhibited RAR-beta expression (16/17, 94% vs. 8/17, 47%, P = 0.003). The RAR-beta expression was seen in the vast majority of the well-differentiated OSCC and in less than half of the moderately differentiated OSCC only (15/20, 75% vs. 7/18, 39%, P = 0.03). CONCLUSION: A correlation between the loss of RAR-beta expression and more advanced histopathological grade tumors was observed. This study also suggests that the loss of RAR-beta expression is significant in BM OSCC, which preferentially occurs in BQ users.

Adult↗

PubMed2002

Rapid in vivo assay for topical oral cancer chemopreventive agents.

The cancer chemopreventive effect of topically applied phenethyl isothiocyanate (PEIT) was examined in a hamster buccal pouch model, in which squamous cell carcinomas (SCC) are induced at high frequency, by topical application of N-methyl-N-benzylnitrosamine (MBN). The buccal pouches of eleven hamsters were pretreated thrice-weekly for two weeks with corn oil (CO) containing 50 mM PEIT, followed by 22 weeks of twice-weekly application of CO containing MBN and PEIT, both at 50 mM. Under similar conditions, twelve hamsters were pretreated with CO for 2 weeks, followed by MBN in CO. Tumor analysis was performed 19 days after the last application of PEIT and MBN. The incidence of tumors (approximately 90% SCC) in the unprotected and protected groups was 100% and 73%, respectively. Although total tumor incidence was marginally decreased, PEIT inhibited significantly the tumor frequency and tumor burden by 79% and 74%, respectively. In both groups, 43% of the carcinomas exhibited p53 immunohistochemical activity. A short-term experiment was performed to determine whether PEIT inhibits MBN-induced cellular foci expressing gamma-glutamyltranspeptidase histochemical activity (gamma-GT foci). Buccal pouches of four protected hamsters received 50 mM PEIT pretreatment on days 1 and 4, followed on days 6 and 9 by application of CO containing MBN and PEIT, both at 50 mM. Four unprotected hamsters were similarly pretreated with CO, followed by MBN in CO. gamma-GT foci were enumerated in buccal pouch epithelial whole mounts prepared from pairs of protected and unprotected hamsters on days 10 through 13. Whereas the number of gamma-GT foci in unprotected hamsters ranged from 98 to 356 per 10 cm2, the protected hamsters exhibited no more than one focus per 10 cm2. This model may be useful for rapid identification of chemopreventive agents, and combinations of agents, which inhibit initiation and promotion stages of oral carcinogenesis.

Administration, Oral↗